The application of cell hybridization technology to immunology by Kohler and Milstein has created revolutionary changes in strategy in investigations in the area of immunology. Although this technology was first applied to obtain monoclonal antibodies against predefined antigens in the murine B lymphocyte system, it recently has been employed to investigate immunoregulatory molecules in the T lymphocyte system. Most laboratories attempting to establish lymphokine secreting T cell hybridomas have used activated or sensitized T cells, which can be obtained by stimulating lymphocytes with mitogenic lectins or antigens. Pathologic lymphocytes can also provide a useful source of valuable immunoregulatory mediators. For example, T cells or thymocytes from patients with immunodeficiency diseases associated with hypo- or agammaglobulinemia may provide a lymphokine source for investigating the abnormalities of immunoregulation and may also provide information on mechanisms involved in normal immunoregulation.
Common variable hypogammaglobulinemia (CVH) is a late onset acquired immunodeficiency disease having the typical feature of significantly reduced levels of all classes of immunoglobulin. Patients with this disease have an increased incidence of sinorespiratory infection such as acute and chronic sinusitis, chronic bronchitis, bronchiectasia and interstitial pneumonia which sometimes cause septicemia. Patients also may have abnormalities of cellular immunity as assessed, by negative delayed hypersensitivity skin tests or depressed responses of peripheral blood lymphocytes to PHA. These patients are prone to produce autoantibodies. This is a paradoxical phenomenon, however, and autoimmune diseases occur with a much greater incidence than in normal individuals. The incidence of CVH with associated thymoma is reported to be about 10%, and about 10% of the cases manifest pure red cell aplasia which is thought to be due to IgG antibody against erythroid stem cells. The pathogenesis of CVH has not been clearly understood, but it has been suggested that suppressor T cells inhibit the maturation of B lymphocytes into antibody secreting plasma cells.